MRI is a well-established technique (in the field of equipments for medical applications), which allows analyzing a body-part of a patient in a substantially non-invasive manner. In general terms, the MRI is based on the application of a high magnetic field to the body-part. As the body-part reacts to the magnetic field in a different way according to its characteristics, by measuring a magnetic response of the body-part it is possible to derive morphological and/or physiological information about it (for example, for the display of a corresponding image).
For this purpose, in a standard MRI technique a magnetic pulse is applied to the body-part so as to alter its magnetization. The magnetization of the body-part then returns to its equilibrium condition with a different relaxation time according to the corresponding characteristics. Therefore, the measure of the magnetization of the body-part while it is returning to the equilibrium condition may be used to represent its characteristics. A contrast agent altering the relaxation time of a specific target region (such as a gadolinium complex) may also be administered to the patient so as to highlight it.
The MRI-CEST technique, instead, exploits a CEST contrast agent (for example, a paramagnetic lanthanide complex) that is capable of transferring its saturated magnetization to the water by chemical exchange. In this case, the measure of this saturation transfer may be used to represent a target region with the CEST agent. For this purpose, a saturation pulse at a resonance frequency of the CEST agent is applied to the body-part, so as to saturate the CEST agent by canceling its magnetization; the saturation transfer then causes a corresponding reduction of the magnetization of the water. Therefore, the saturation transfer may be measured by comparing the magnetization of the body-part at the resonance frequency of the LEST agent with a reference value representing the magnetization of the body-part alone (i.e., without the CEST agent); since the magnetic response of the body-part alone is substantially symmetric around a resonance frequency of the water, the reference value may be defined by the magnetization of the body-part at a reference frequency opposite the resonance frequency of the CEST agent with respect to the resonance frequency of the water. For example, the MRI-CEST technique is described in “Ward K M, Aletras A H, Balaban R S, “A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST),” J Magn Reson. 2000; 143(1):79-87” (the entire disclosure of which is herein incorporated by reference).
The MRI-CEST technique allows enabling the CEST agent selectively (by means of the saturation pulse of the CEST agent at the corresponding resonance frequency); therefore, it may also be possible to obtain images representing more CEST agents in the same body-part. Moreover, the desired information is obtained directly from the magnetic response of the body-part—without the need of comparing the acquired image with a background image without any contrast agent as in the (standard) MRI technique.
Several studies about possible applications of the MRI-CEST technique have been reported; for example, the MRI-CEST technique has been proposed for pH measurements, cell labeling, imaging of diagnostic markers like glucose, lactate and zinc, visualization of enzyme activity, and monitoring of gene expression.
Nevertheless, the MRI-CEST technique still suffers from some drawbacks that make its practical exploitation challenging. Particularly, errors may occur in the measurement of the saturation transfer because of spillover effects (causing an unwanted magnetization diffusion) when the resonance frequency of the CEST agent is too close to the resonance frequency of the water. Another source of errors is any asymmetry in the magnetic response of the body-part (caused by natural magnetization transfers in the body-part). Moreover, further errors may arise from differences of an actual offset of the resonance frequency of the CEST agent from the resonance frequency of the water with respect to its theoretical value (caused by heterogeneities of the body-part). Additional errors may be due to non-optimal shimming and tuning, signal damping, inhomogeneity of the magnetic field, and shifts and deformations due to involuntary motions of the body-part.
Therefore, the MRI-CEST techniques known in the art provide a relatively poor Contrast-to-Noise Ratio (CNR) for the detection of the target regions. All of the above limits the accuracy of the MRI-CEST technique (with possible false detections of the target regions) and its sensitivity (resulting in missing detections of the target regions).